Various recombinant and nonrecombinant interferons have been tested in Phase I trials in cancer patients in order to study the toxicity, antitumor effects, immunomodulatory effects and pharmacokinetics of these preparations. The initial Phase I trials employed highly purified recombinant leukocyte A interferon and human Namalva cell lymphoblastoid interferon. These trials, which are now complete, demonstrated that both interferons could be administered safely to patients with disseminated cancer and that the toxicities encountered resembled those previously reported for less purified Cantell alpha interferon. Antitumor responses were seen in 9 or 76 evaluable patients treated with recombinant interferon. These 9 patients included 5 patients with non-Hodgkin's lymphoma, and 1 patient each with chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and malignant melanoma. Three of 39 evaluable patients responded to lymphoblastoid interferon, including patients with undifferentiated carcinoma of the pelvis, nodular lymphoma, and hypernephroma. Pharmacokinetic analysis revealed dose-dependent levels of serum interferon activity. Immunologic monitoring data indicate unchanged or decreased natural killer cell mediated cytotoxicity, increased monocyte function in a growth inhibition assay and decreased lymphocyte blastogenesis. Other Phase I interferon trials recently initiated include trials of recombinant leukocyte A interferon as an intralesional agent and escalating dose trials of nonrecombinant gamma (immune) interferon and recombinant beta (fibroblast) interferon.